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Society of Nuclear Medicine Procedure Guideline for

Brain Death Scintigraphy
version 1.0, approved February 25, 2003

Authors: Kevin J. Donohoe, MD (Beth Israel Deaconess Medical Center, Boston, MA); Kirk A. Frey, MD, PhD (University
of Michigan Medical Center, Ann Arbor, MI); Victor H. Gerbaudo, PhD (Brigham and Women’s Hospital, Boston, MA);
Giuliano Mariani, MD (University of Pisa Medical School, Pisa, Italy); James S. Nagel, MD (Veterans Affairs Boston Health-
care System, West Roxbury, MA); and Barry Shulkin, MD (University of Michigan Medical Center, Ann Arbor, MI).

I. Purpose blood flow. However, a tourniquet should not
be used in patients with a history of head
The purpose of this guideline is to assist nuclear
trauma when there is a concern that the
medicine practitioners in recommending, perform-
tourniquet will exacerbate the injury. A
ing, interpreting, and reporting the results of brain
tourniquet may also raise intracranial pres-
perfusion imaging to assist in confirming the diag-
sure and, therefore, should not be used unless
nosis of brain death.
there is adequate monitoring of intracranial
pressure or there is little reason to expect an
II. Background Information and Definitions elevation of intracranial pressure.
4. Patients should be normally ventilated to pre-
The diagnosis of brain death is a clinical diagnosis
vent changes in cerebral blood flow that may
that is sometimes made with the help of cerebral per-
be caused by hyperventilation.
fusion scintigraphy. It is important that all physi-
cians be knowledgeable in the clinical requirements B. Information Pertinent to Performing the Proce-
for the diagnosis of brain death, especially the need dure
to establish irreversible cessation of all function of 1. History of head trauma or central nervous
the cerebrum and brain stem. Institutions perform- system (CNS) injury should be obtained.
ing scintigraphy for the evaluation of possible brain Trauma or focal CNS ischemia or infection
death should develop clinical guidelines and proce- may cause abnormalities in blood flow that
dures for the clinical diagnosis that incorporate both may complicate image interpretation.
clinical evaluations and the integration of ancillary 2. It should be determined whether the patient
tests such as perfusion scintigraphy. can be positioned as needed for brain perfu-
sion imaging. Anterior or posterior images
should be properly aligned so that symmetry
III. Common Indications of blood flow to both sides of the head and su-
A. Assess brain blood flow in patients suspected of perior sagittal sinus activity can be assessed.
brain death. 3. Care should be taken to note whether the pa-
tient has recently received barbiturates. At
high levels, these agents may decrease cere-
IV. Procedure bral blood flow.
A. Patient Preparation C. Precautions
1. No special preparation is necessary. None
2. The patient should have a stable blood pres- D. Radiopharmaceutical
sure, and all correctable major systemic bio- Several 99mTc-labeled agents may be used, in-
chemical abnormalities should be addressed. cluding:
3. In some institutions, a tourniquet is placed 1. 99mTc-ethyl cysteinate dimer (99mTc-ECD)
around the scalp, encircling the head just 2. 99mTc-hexamethylpropylene amine oxime
above the eyebrows, ears, and around the (99mTc-HMPAO)
posterior prominence of the skull. The tourni- 3. 99mTc-diethylenetriaminepentaacetic acid
quet can help diminish scalp blood flow, pre- (99mTc-DTPA)
venting it from being confused with brain Although brain-specific tracers such as 99mTc-
114 • BRAIN DEATH SCINTIGRAPHY

Radiation Dosimetry in Adults

Radiopharmaceuticals Administered Activity Organ Receiving the Effective Dose
Largest Radiation Dose
MBq MGy/MBq MSv/MBq
(mCi) (rad/mCi) (rem/mCi)
99m
Tc-DTPA1 555–740 0.065 0.0063
intravenously Bladder wall
(15–20) (0.24) (0.023)
99m
Tc-HMPAO2 370–1,110 0.034 0.0093
intravenously Kidneys
(10–30) (0.0126) (0.034)
99m
Tc-ECD3 370–1,110 0.073 0.011
intravenously Bladder wall
(10-30) (0.27) (0.042)
1
International Commission on Radiological Protection and Measurements. Radiation Dose to Patients from Radiophar-
maceuticals. ICRP report no. 53. London, UK: ICRP; 1988:188.
2
International Commission on Radiological Protection and Measurements. Radiological Protection in Biomedical Re-
search. ICRP report no. 62. London, UK: ICRP; 1993:13.
3
Oak Ridge Institute for Science and Education. Radiation Dose Estimates for Radiopharmaceuticals. Oak Ridge, TN: Radi-
ation Internal Dose Information Center. Available at: www.orau.gov/ehsd/DOSETABLES.doc. Accessed Feb.13, 2003.

HMPAO and 99mTc-ECD are increasing in popu- tra-high resolution (UHR) collimator.
larity, there is no clear evidence they are more ac- c. 15%–20% energy window centered around
curate than nonspecific agents. Brain-specific 140 keV.
agents are preferred by some institutions, be- 2. Flow images are acquired at the time of tracer
cause their interpretation is far less dependent injection.
on the quality of the bolus and because delayed a. 1–3 s per frame for at least 60 s. Flow im-
images are usually definitive for the presence or ages should start before the arrival of the
absence of cerebral blood flow. bolus in the neck and end well after the ve-
The Brain Imaging Council of the Society of nous phase.
Nuclear Medicine believes that although individ- b. Use of high-resolution or UHR collimation
ual laboratories may have used and may continue is recommended. As a general rule, use the
to use agents such as DTPA, glucoheptonate, and highest resolution collimation available.
pertechnetate (with perchlorate blockade), these 3. Static images
are much less favorable than HMPAO and ECD a. If a non-brain-binding agent, such as 99mTc-
for assessment of cerebral perfusion. DTPA, is used, static images are acquired
E. Image Acquisition immediately for 5 min in anterior, right lat-
Flow images should be acquired. They are essen- eral, left lateral, and, if possible, posterior
tial for interpretation of studies using non-brain- projections for approximately 5 min per
binding agents such as 99mTc-DTPA. In studies view. Zooming or magnification may be
using brain-specific agents, such as 99mTc-HM- helpful, particularly in pediatric cases.
PAO and 99mTc-ECD, lack of visualization of the b. For brain-specific agents, planar and
brain on delayed images could conceivably be SPECT images should be obtained after at
caused by improper preparation or instability of least 20 min. Images should be obtained in
the radiopharmaceutical. Flow images will help anterior, right lateral, left lateral, and, if
to confirm lack of brain blood flow when the possible, posterior projections.
brain is not visualized on delayed images using 4. When using brain-specific agents, such as
99m
99m
Tc-HMPAO and 99m Tc-ECD. Tc-HMPAO and 99mTc-ECD, SPECT im-
1. Instrumentation ages may be obtained in addition to flow and
a. Gamma camera with field of view large planar images as described above. SPECT al-
enough to image entire head and neck. lows better visualization of perfusion to the
b. Low-energy high-resolution (LEHR) or ul- posterior fossa and brain stem structures.
SOCIETY OF NUCLEAR MEDICINE PROCEDURE GUIDELINES MANUAL MARCH 2003 • 115

Radiation Dosimetry in Children
(5 Years Old; Normal Renal Function)

Radiopharmaceuticals Administered Activity Organ Receiving the Effective Dose
Largest Radiation Dose
MBq/kg Minimum Maximum MGy/MBq MSv/MBq
Dose Dose Dose
(mCi/kg) MBq MBq
(rad/mCi) (rem/mCi)
(mCi) (mCi)
99m
Tc-DTPA1 7.4 370 740 0.17 0.017
intravenously (10) (20) Bladder wall
(0.2) (0.63) (0.063)
99m
Tc-HMPAO2 11.1 185 740 0.14 0.026
intravenously (5) (20) Thyroid
(0.3) (0.52) (0.096)
99m
Tc-ECD3 11.1 185 740 0.083 0.023
intravenously (5) (20) Bladder wall
(0.3) (0.31) (0.085)
1
International Commission on Radiological Protection and Measurements. Radiation Dose to Patients from Radiophar-
maceuticals. ICRP report no. 53. London, UK: ICRP; 1988:188.
2
International Commission on Radiological Protection and Measurements. Radiological Protection in Biomedical Re-
search. ICRP report no. 62. London, UK: ICRP; 1993:13.
3
Oak Ridge Institute for Science and Education. Radiation Dose Estimates for Radiopharmaceuticals. Oak Ridge, TN: Ra-
diation Internal Dose Information Center. Available at: www.orau.gov/ehsd/pedose.doc. Accessed Feb. 13, 2003.

However, SPECT is rarely, if ever, used in amount of tracer activity in the brain and
these patients who are often unstable and on the specific camera being used. It is sug-
life support equipment, which may be incom- gested that the number of seconds per stop
patible with SPECT acquisition. be similar to that used on your equipment
a. Multiple-detector or other dedicated for acquiring other brain SPECT studies.
SPECT cameras generally produce results g. It is frequently useful to use detector pan
superior to single-detector, general-pur- and zoom capabilities to ensure that the en-
pose units. However, with meticulous at- tire brain is included in the field of view
tention to procedure, high-quality images while allowing the detector to clear the pa-
can be produced on single-detector units tient’s shoulders.
with appropriately longer scan times (5 x F. Interventions
106 total counts or more are desirable). None
b. LEHR or fanbeam collimators are pre- G. Processing: SPECT
ferred when SPECT images will be ac- 1. Filter studies in 3 dimensions. This can be
quired. As a general rule, use the highest achieved either by 2-dimensionally prefilter-
resolution collimation available. ing the projection data or by applying a 3-di-
c. Use the smallest possible radius of rotation. mensional postfilter to the reconstructed data.
d. A 128 x 128 or greater acquisition matrix is 2. Low-pass (e.g., Butterworth) filters should be
preferred. used. Resolution recovery or spatially varying
e. Angular sampling of 3° or better is pre- the filters should be used with caution, how-
ferred. Acquisition pixel size should be ever; they may produce artifacts.
1/3–1/2 the expected reconstructed reso- 3. Always reconstruct the entire brain. Use care
lution. It may be necessary to use a hard- not to exclude the cerebellum or vertex.
ware zoom to achieve an appropriate pixel 4. Reconstruct data at highest pixel resolution
size. Different zoom factors may be used (i.e., 1 pixel thick). If slices are to be summed,
with in-plane and axial dimensions of a this should be done only after reconstruction
fanbeam collimator. and oblique reorientation (if performed).
f. The time per stop and number of counts ac- H. Interpretation Criteria
quired for the study will depend on the 1. For studies using brain-specific agents:
116 • BRAIN DEATH SCINTIGRAPHY

a. Flow images in brain death are character- well as pressure on the portion of the
ized by a lack of flow to the middle cerebral scalp resting on a hard surface, can
artery, the anterior cerebral artery, and the produce a relatively photopenic area
posterior cerebral artery. This often results on the flow study, falsely suggesting
in a lack of a “blush” of activity in the mid- diminished flow.
dle of the head during flow images. Keep c. Delayed planar or SPECT images should
in mind that the external carotid artery will demonstrate no tracer uptake in the brain
likely remain patent and there will be some for the diagnosis of brain death to be made.
flow to the scalp, which can be mistaken For SPECT studies, unprocessed projection
for brain flow in some instances. Another images should be reviewed in cinematic
important sign in brain death is lack of display before viewing of tomographic sec-
tracer activity in the superior sagittal sinus tions. Projection data should be assessed
during the venous phase of the flow study. for target-to-background ratio and other
b. Flow images are assessed for blood flow to potential artifacts. Inspection of the projec-
the brain. tion data in sinogram form may also be
(1) Anterior views are preferred for imag- useful. The role and use of SPECT imaging
ing blood flow. The head should be is unclear. Both cerebral hemispheres and
viewed straight on to allow for com- the posterior fossa (cerebellum) should be
parison of right and left carotid flow. evaluated for a complete study. Therefore,
(2) Tracer flow should be observed from if performing planar scintigraphy an ante-
the level of the carotids to the skull ver- rior-posterior or posterior-anterior view,
tex. In the anterior position, the right separating left and right hemispheres and
and left middle cerebral arteries appear at least 1 lateral view to distinguish the
along the lateral aspects of the skull. cerebral flow from that of the cerebellum
The anterior cerebral arteries appear are commonly needed.
midline and appear as 1 vessel. d. Images viewed on a computer screen
(3) In brain death, blood flow superior to rather than from film or paper copy permit
the circle of Willis circulation is com- interactive adjustment of contrast, back-
pletely absent. There may be an accom- ground subtraction, and color table.
panying blush of activity in the region e. Grayscale is preferred to color tables. At
of the nose (“hot nose sign”). Care very low levels of activity, color tables usu-
must be taken to distinguish external ally designed for viewing near-normal ac-
carotid circulation to the scalp from in- tivity may under-represent low activity,
ternal carotid circulation to the brain. causing a false-positive study.
(4) The superior sagittal sinus is often 2. For studies using non-brain-binding agents
noted during the venous phase of a. Delayed images using agents that are not
blood flow in patients with intact blood brain specific should not demonstrate su-
flow to the brain. However, low-level perior sagittal sinus activity in patients
sagittal sinus activity can come from with brain death. Another finding that
the scalp. If no internal carotid flow or may be present in patients with brain
CNS perfusion is seen on the flow death is the “halo” sign. This is a pho-
study and minimal sagittal sinus activ- topenic defect caused by compression of
ity is noted, these findings should be scalp blood flow that may be seen when
noted and a note of caution regarding the patient’s head is resting on a firm ob-
the accuracy of the interpretation in- ject, such as an imaging table.
cluded in the report. I. Reporting
(5) In cases of head trauma, hyperemic 1. Reports should include the tracer used and ba-
blood flow to injured scalp structures sic imaging information, such as the acquisition
may mimic brain blood flow or supe- of SPECT and/or planar images. Flow images
rior sagittal sinus activity. should be reported in a separate paragraph.
(6) CSF shunts and intracranial pressure 2. Reports should describe the extent and sever-
transducers can cause hyperemia re- ity of brain perfusion deficits. If brain-specific
sulting in increased scalp flow, possi- agents are used, specific mention of perfusion
bly causing a false-negative flow study. to the posterior fossa and brain stem may be
Disruptions in the skull and scalp, as reported. Because this study is used in combi-
SOCIETY OF NUCLEAR MEDICINE PROCEDURE GUIDELINES MANUAL MARCH 2003 • 117

nation with other tests and physical exam Neuroradiology. 1995;375:365–369.
findings, the final impression of a positive Facco E, Zucchetta P, Munari M, et al. 99mTc-HM-
study should state that the study is “consis- PAO SPECT in the diagnosis of brain death. In-
tent with brain death” rather than “demon- tensive Care Med. 1998;249:911–917.
strates brain death.” Flowers WM, Jr., Patel BR. Accuracy of clinical eval-
3. Severely decreased brain perfusion is often uation in the determination of brain death. South
progressive. If there is a small amount of re- Med J. 2000;93:203–206.
maining perfusion, consider recommending a Haupt WF, Rudolf J. European brain death codes: a
repeat study in 24 h. comparison of national guidelines. J Neurol.
J. Quality Control 1999;246:432–437.
1. If using brain-specific agents, quality control Hoch DB. Brain death: a diagnostic dilemma. J Nucl
of labeling and stability of the compound is Med. 1992;33:2211–2213.
essential to prevent false-positive results. Larar GN, Nagel JS. Tc-99m HMPAO cerebral perfu-
Poor radiopharmaceutical labeling or stability sion scintigraphy: considerations for timely
would result in minimal concentration of brain death declaration. J Nucl Med.
tracer in the brain. This could be falsely inter- 1992;33:2209–2211.
preted as lack of cerebral perfusion. Lee VW, Hauck RM, Morrison MC, Peng TT, Fischer
2. See Society of Nuclear Medicine Procedure Guide- E, Carter A. Scintigraphic evaluation of brain
line for General Imaging. death: significance of sagittal sinus visualization.
K. Sources of Error J Nucl Med. 1987;28:1279–1283.
1. Improper labeling of brain-specific radio- Lopez-Navidad A, Caballero F, Domingo P, et al.
pharmaceuticals or injection of the wrong ra- Early diagnosis of brain death in patients treated
diopharmaceutical can result in false-positive with central nervous system depressant drugs.
studies as described in section J.1. Transplantation. 2000;70:131–135.
2. Drainage of blood from the scalp into the su- Mrhac L, Zakko S, Parikh Y. Brain death: the evalu-
perior sagittal sinus may cause a false-nega- ation of semi-quantitative parameters and other
tive flow study. signs in HMPAO scintigraphy. Nucl Med Com-
3. Hyperemic scalp structures may result in mun. 1995;16:1016–1020.
false-negative flow studies if non-specific Spieth M, Abella E, Sutter C, Vasinrapee P, Wall L,
brain agents are used. Ortiz M. Importance of the lateral view in the
4. Infiltration of tracer at injection site may cause evaluation of suspected brain death. Clin Nucl
a false-positive study if the entire dose is infil- Med. 1995;20:965–968.
trated and not available to the vascular space.
Absence of activity in the carotid vessels on
VII. Disclaimer
flow images suggests complete infiltration of
the dose. The Society of Nuclear Medicine has written and
approved guidelines to promote the cost-effec-
tive use of high-quality nuclear medicine proce-
V. Issues Requiring Further Clarification
dures. These generic recommendations cannot
A. The relative accuracies of brain-specific and non- be applied to all patients in all practice settings.
specific agents. The guidelines should not be deemed inclusive
B. The importance of SPECT imaging. of all proper procedures or exclusive of other
C. The value of brain-specific agents for the detec- procedures reasonably directed to obtaining the
tion of small areas of brain perfusion, such as in same results. The spectrum of patients seen in a
the posterior fossa. Will this increased sensitivity specialized practice setting may be quite differ-
for small areas of perfusion change the ultimate ent from the spectrum of patients seen in a more
prognosis? general practice setting. The appropriateness of
D. The influence of open fontanels in small children a procedure will depend in part on the preva-
upon the accuracy of flow studies. lence of disease in the patient population. In ad-
dition, the resources available to care for pa-
tients may vary greatly from one medical facility
VI. Concise Bibliography
to another. For these reasons, guidelines cannot
Bonetti MG, Ciritella P, Valle G, Perrone E. 99m-Tc be rigidly applied.
HM-PAO brain perfusion SPECT in brain death.